Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003328364 | SCV001142230 | pathogenic | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-04 | reviewed by expert panel | curation | The c.315delC p.(Thr106Profs) variant is predicted to result in a premature stop codon that leads to nonsense mediate decay (PVS1 and PM5_supporting). The variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). Therefore, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (CDH1 VCEP specifications version 3.1): PVS1, PM2_supporting, PM5_supporting. |
Gene |
RCV000486371 | SCV000571755 | likely pathogenic | not provided | 2016-10-14 | criteria provided, single submitter | clinical testing | This deletion of one nucleotide in CDH1 is denoted c.315delC at the cDNA level and p.Thr106ProfsX11 (T106PfsX11) at the protein level. The normal sequence, with the base that is deleted in braces, is ACTC[C]ACCT. The deletion causes a frameshift which changes a Threonine to a Proline at codon 106, and creates a premature stop codon at position 11 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available information, we consider this deletion to be a likely pathogenic variant. |
Ambry Genetics | RCV002323838 | SCV002608472 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-06-14 | criteria provided, single submitter | clinical testing | The c.315delC pathogenic mutation, located in coding exon 3 of the CDH1 gene, results from a deletion of one nucleotide at nucleotide position 315, causing a translational frameshift with a predicted alternate stop codon (p.T106Pfs*11). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Myriad Genetics, |
RCV003335370 | SCV004044074 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2023-06-08 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
Labcorp Genetics |
RCV003335370 | SCV004487259 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2022-12-15 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 422315). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr106Profs*11) in the CDH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDH1 are known to be pathogenic (PMID: 15235021, 20373070). |